Meniere’s Attacks Occur in the Inner Ear with Excessive Vasopressin Type‐2 Receptors

Abstract

Meniere's disease is peculiar to humans and is characterised by episodic vertigo, fluctuating hearing loss and tinnitus, and attacks of the affliction occurring under conditions of stress. Its pathology was first revealed to be inner ear hydrops through temporal bone studies in 1938. Although subsequently proposed as a disorder of water metabolism in the inner ear, its pathogenesis remains unsolved. The present study aimed to assess the link between the inner ear pathology in Meniere's disease and vasopressin, an anti-diuretic stress hormone with a potential role in inner ear fluid homeostasis. Blood samples were obtained from Meniere's disease patients in the morning, before any surgical treatment, to examine plasma vasopressin (pAVP) levels, and then from inner ear tissue during surgical treatment, to examine vasopressin type-2 receptor (V2R) in the endolymphatic sac. pAVP and the relative V2R mRNA expression in the endolymphatic sac were examined using a real-time polymerase chain reaction. Relative cAMP activity in the endolymphatic sac was also examined using tissue culture and cAMP assay. Both pAVP (1.6-fold versus controls; P = 0.048) and inner ear V2R mRNA expression (41.5-fold versus controls; P = 0.022) were significantly higher in Meniere's patients. cAMP activity was basally up-regulated (2.1-fold versus controls) and cAMP sensitivity to vasopressin application was largely elevated (4.9-fold versus controls) in Meniere's patients. We conclude that, in the pathogenesis of inner ear hydrops, resulting in Meniere's attacks, elevation of pAVP levels (probably as a result of stress) may present as a matter of consequence, but susceptibility of the V2R-overexpressed and cAMP-hypersensitized inner ear to pAVP elevation might be essential as the basis of this disease. Further experimental and clinical studies are needed to better clarify the relationship between Meniere's disease and stress.

Plasma Vasopressin and V2 Receptor in the Endolymphatic Sac in Patients With Delayed Endolymphatic Hydrops

“…Furthermore, the hypothesis of a high level of pAVP, which should have equal effects on both ears, contradicts the fact that 70% to 80% of patients with MD are unilateral (16). In fact, there were no significant differences between the pAVP levels in patients with unilateral and bilateral MD in our recent study (17). Therefore, the above hypothesis is insufficient for explaining the pathogenesis of endolymphatic hydrops, which has remained unsolved since endolymphatic hydrops was demonstrated in patients with MD in 1938 (3,4) and in patients with DEH in 1976 (2).…”

Endolymphatic sac tumor with overexpression of V2 receptor mRNA and inner ear hydrops

“…These findings suggest that MD-like symptoms could be due to inner ear hydrops [13,14] induced by ELSTs. Furthermore, the molecular biological examination also revealed that V2R mRNA expression in the endolymphatic sac of both cases of ELST was up-regulated, as seen in MD, compared with controls of VS [5,7]. Based on our recent molecular biological studies in the endolymphatic sac of MD [5,6] and delayed endolymphatic hydrops [7], there was a strong relationship between the pathogenesis of inner ear hydrops and the intracellular signal cascade of V2R in the endolymphatic sac.…”

“…Furthermore, the molecular biological examination also revealed that V2R mRNA expression in the endolymphatic sac of both cases of ELST was up-regulated, as seen in MD, compared with controls of VS [5,7]. Based on our recent molecular biological studies in the endolymphatic sac of MD [5,6] and delayed endolymphatic hydrops [7], there was a strong relationship between the pathogenesis of inner ear hydrops and the intracellular signal cascade of V2R in the endolymphatic sac. All these findings suggest that the inflammation in the endolymphatic sac in case 1 and the tumor pressure in the endolymphatic sac of case 2 might have an effect on the endolymphatic environment, probably through the overexpression of V2R mRNA in the endolymphatic sac.…”

“…Based on our recent molecular biological studies of the endolymphatic sac in MD [5,6] and delayed endolymphatic hydrops [7], strong relationships were revealed between the pathogenesis of inner ear hydrops and the intracellular signal cascade of antidiuretic stress hormone vasopressin type-2 receptor (V2R) in the endolymphatic sac. Therefore, in the present ELST study, we focused on V2R expression in the endolymphatic sac.…”

Functional Expression of an Osmosensitive Cation Channel, Transient Receptor Potential Vanilloid 4, in Rat Vestibular Ganglia

“…Aquaporin 2 (AQP2) and vasopressin type 2 receptor (V2R) are also expressed in the epithelial layer of the endolymphatic sac and VG [Takumida et al, 2012]. Patients with Ménière's disease show elevated expression of plasma vasopressin and V2R in the endolymphatic sac [Kitahara et al, 2008]. Indeed, plasma vasopressin elevation, subsequent activation of V2R-cAMP-protein kinase A-AQP2, and endosomal trapping of AQP2 in the endolymphatic sac might be important in the pathogenesis of endolymphatic hydrops, resulting in Ménière's attacks [Maekawa et al, 2010].…”